The studies proposed are aimed at investigating in vitro and in vivo immune responses to mouse mammary tumor virus (MTV) during the latent period prior to spontaneous tumor development. We have shown in previous studies that MTV-infected mice are not tolerant to MTV and that immune reactivity to MTV depends upon the dose, route and length of exposure to MTV antigens. We will further investigate macrophage and lymphocyte functions in animals developing mammary tumors, employing three different mouse strain models, C3H, RIII and GR. One major aim of this project will be to investigate the hypothesis that suppressor mechanisms induced by MTV infection play a role in the oncogenic process of MTV. Relevant to this, we recently obtained results suggesting suppression of some immune responses in animals exhibiting immune reactivity against MTV. This supports previous data showing that immunosuppression induced by neonatal thymectomy or by injection of antilymphocyte serum delays the appearance and reduces the incidence of spontaneous mammary tumors in mice. Taken together, these results suggest that some aspects of the immune response may play a role in the formation of spontaneous mammary tumors. On the basis of the information obtained concerning the biology of the MTV system, we will attempt to induce more effective resistance to progressive tumor growth by pharmacological modulation of the immune reactions associated with MTV infection. For this purpose we will employ immunosuppresive and immunostimulant agents and will determine what changes in immune reactivity alter the incidence or progressive growth of spontaneous mammary tumors. The experimental findings are expected to be useful in further understanding the biology of human breast cancer, which has many aspects in common with mouse mammary tumors induced by MTV.